Linked Life Data

19629143

Source:http://linkedlifedata.com/resource/pubmed/id/19629143

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-1-19
pubmed:abstractText
Targeted oncolytic poxviruses hold promise for the treatment of cancer. Arming these agents with immunostimulatory cytokines (for example, granulocyte-monocyte colony-stimulating factor; GM-CSF) can potentially increase their efficacy and/or alter their safety. However, due to species-specific differences in both human GM-CSF (hGM-CSF) activity and poxviruses immune avoidance proteins, the impact of hGM-CSF expression from an oncolytic poxvirus cannot be adequately assessed in murine or rat tumor models. We developed a rabbit tumor model to assess toxicology, pharmacodynamics, oncolytic efficacy and tumor-specific immunity of hGM-CSF expressed from a targeted oncolytic poxvirus JX-963. Recombinant purified hGM-CSF protein stimulated a leukocyte response in this model that paralleled effects of the protein in humans. JX-963 replication and targeting was highly tumor-selective after i.v. administration, and intratumoral replication led to recurrent, delayed systemic viremia. Likewise, hGM-CSF was expressed and released into the blood during JX-963 replication in tumors, but not in tumor-free animals. hGM-CSF expression from JX-963 was associated with significant increases in neutrophil, monocyte and basophil concentrations in the peripheral blood. Finally, tumor-specific cytotoxic T lymphocytes (CTL) were induced by the oncolytic poxvirus, and expression of hGM-CSF from the virus enhanced both tumor-specific CTL and antitumoral efficacy. JX-963 had significant efficacy against both the primary liver tumor as well as metastases; no significant organ toxicity was noted. This model holds promise for the evaluation of immunostimulatory transgene-armed oncolytic poxviruses, and potentially other viral species.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19629143-10505851, http://linkedlifedata.com/resource/pubmed/commentcorrection/19629143-1509275, http://linkedlifedata.com/resource/pubmed/commentcorrection/19629143-15621303, http://linkedlifedata.com/resource/pubmed/commentcorrection/19629143-16397056, http://linkedlifedata.com/resource/pubmed/commentcorrection/19629143-16905462, http://linkedlifedata.com/resource/pubmed/commentcorrection/19629143-17383529, http://linkedlifedata.com/resource/pubmed/commentcorrection/19629143-17693992, http://linkedlifedata.com/resource/pubmed/commentcorrection/19629143-17965776, http://linkedlifedata.com/resource/pubmed/commentcorrection/19629143-1856212, http://linkedlifedata.com/resource/pubmed/commentcorrection/19629143-18628758, http://linkedlifedata.com/resource/pubmed/commentcorrection/19629143-3497952, http://linkedlifedata.com/resource/pubmed/commentcorrection/19629143-7545029, http://linkedlifedata.com/resource/pubmed/commentcorrection/19629143-7883967
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1476-5500
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
73-9
pubmed:dateRevised
2010-9-27
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Oncolytic and immunostimulatory efficacy of a targeted oncolytic poxvirus expressing human GM-CSF following intravenous administration in a rabbit tumor model.
pubmed:affiliation
Department of Radiology, College of Medicine, Dong-A University, Busan, South Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't